Typically, compounds of formula I are prepared by reacting, for example, b-chloroethylpiperidine hydrochloride and ethyl 4-hydroxybenzoate in methyl ethyl ketone, in the presence of potassium carbonate (see, U.S. Pat. No. 4,418,068.) However, the referenced synthetic route has certain undesirable aspects. Firstly, the solvent, methyl ethyl ketone, is hazardous and requires expensive handling and disposal procedures. Secondly, use of this solvent sets a limit of 80.degree. C. as a reaction temperature during formation of an ester, thus limiting the rate of the potassium carbonate catalyzed alkylation reaction. Furthermore, the organic layer containing the ester must be stripped to an oil prior to dissolution of the oil in aqueous sodium hydroxide and methanol. This oil preparation step is time consuming and could reduce the ultimate yield with large-scale production.
Thus, a more efficient, less expensive process for preparing compounds of formula I, and, ultimately, compounds of formula II, especially if such an efficient process did not require the use of hazardous solvents, would be a significant and desirable advance over the current state of the art. The present invention provides such a process.
Analogously, Yoshino, et al., Bulletin of the Chemical Society of Japan, 46:553-556 (1973), disclose condensation reactions of ethylene carbonate with a variety of phenols in the presence of tetraethylammonium halides or a metal hydride such as lithium or sodium hydride. These reactions generally are run in the presence of dimethylformamide (DMF) as a solvent, the presence of which creates considerable limitations. Most importantly, the use of DMF would require the isolation of each intermediate compound prepared by the process of the present invention prior to the commencement of the subsequent step. The replacement of DMF with a solvent which would allow each step of the present processes to be run without isolating each intermediate would provide a significant advance to the present state of the art. Such an advance is provided by the present processes.